caa a22 4500 445312564 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0512-8 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0512-8 Effect of Sugars on the Molecular Motion of Freeze-Dried Protein Formulations Reflected by NMR Relaxation Times [Elektronische Daten] [Sumie Yoshioka, Kelly Forney, Yukio Aso, Michael Pikal] ABSTRACT: Purpose: To relate NMR relaxation times to instability-related molecular motions of freeze-dried protein formulations and to examine the effect of sugars on these motions. Methods: Rotating-frame spin-lattice relaxation time (T1ρ) was determined for both protein and sugar carbons in freeze-dried lysozyme-sugar (trehalose, sucrose and isomaltose) formulations using solid-state 13C NMR. Results: The temperature dependence of T1ρ for the lysozyme carbonyl carbons in lysozyme with and without sugars was describable with a model that includes two different types of molecular motion with different correlation times (τc) for the carbon with each τc showing Arrhenius temperature dependence. Both relaxation modes have much smaller relaxation time constant (τc) and temperature coefficient (Ea) than structural relaxation and may be classified as β-relaxation and γ-relaxation. The τc and Ea for γ-relaxation were not affected by sugars, but those for β-relaxation were increased by sucrose, changed little by trehalose, and decreased by isomaltose, suggesting that the β-mobility of the lysozyme carbonyl carbons is decreased by sucrose and increased by isomaltose. Conclusion: T1ρ determined for the lysozyme carbonyl carbons can reflect the effect of sugars on molecular mobility in lysozyme. However, interpretation of relaxation time data is complex and may demand data over an extended temperature range. Springer Science+Business Media, LLC, 2011 freeze-dried protein nationallicence molecular dynamics nationallicence NMR nationallicence relaxation time nationallicence sucrose nationallicence Yoshioka Sumie School of Pharmacy, University of Connecticut, 06269-3092, Storrs, Connecticut, USA aut Forney Kelly School of Pharmacy, University of Connecticut, 06269-3092, Storrs, Connecticut, USA aut Aso Yukio National Institute of Health Sciences, Setagaya, 158-8501, Tokyo, Japan aut Pikal Michael School of Pharmacy, University of Connecticut, 06269-3092, Storrs, Connecticut, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3237-3247 0724-8741 28:12<3237 2011 28 11095 https://doi.org/10.1007/s11095-011-0512-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0512-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yoshioka Sumie School of Pharmacy, University of Connecticut, 06269-3092, Storrs, Connecticut, USA aut NATIONALLICENCE 700 1- Forney Kelly School of Pharmacy, University of Connecticut, 06269-3092, Storrs, Connecticut, USA aut NATIONALLICENCE 700 1- Aso Yukio National Institute of Health Sciences, Setagaya, 158-8501, Tokyo, Japan aut NATIONALLICENCE 700 1- Pikal Michael School of Pharmacy, University of Connecticut, 06269-3092, Storrs, Connecticut, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3237-3247 0724-8741 28:12<3237 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer